Deficiencies of T lymphocyte function in humans may contribute to the pathogenesis of autoimmune diseases, various maligancies and even to the process of aging. New Zealand Black (NZB) and NZB/NZW F1 (B/W) mice are genetically predisposed to a progressive disorder of immunologic regulation associated with the development of autoimmunity and lymphoid malignancies. Immunological abnormalities in NZB mice and in patients with autoimmune diseases are accompanied by a decrease in suppressor T cells and a deficit in circulating thymic hormone. Graft vs. host experiments with NZB and B/W mice have suggested a possible requirement for a thymic differentiation hormone in order to maintain the integrity and function of suppressor T cells. In this proposal, we plan to examine mononuclear cells reactive with autologous erythrocytes that are abundant in the peritoneal cavity of NZB mice. We will study the contributions of T cells, B cells and macrophages to the formation of rosettes and plaques with autologous red cells in NZB and control strains. Our preliminary results suggest a release of immunoregulatory control when normal lymphocytes are placed in in vitro culture conditions, possibly reflecting a loss of suppressor T cells. We will use this assay system to study the ability of thymosin and other thymic humoral factors to restore immunoregulation. These studies will be extended to humans, and will also involve other autoantigens. They should lead to a better understanding of the normal processes of immunologic regulation.